2-amino-4-nitropyridines

If 2- and 4-aminopyridines are diazotized in dilute mineral acids, diazonium salts are formed however, the diazonium ions are not stable and they hydrolyze rapidly to the corresponding pyridones. " For example, the diazotization of 2-amino-4-nitropyridine in sulfuric acid yields 85% of 4-nitro-2-pyridone. Diazonium salts of 2-substituted-4-aminopyridines with electron-withdrawing substituents such as COOH, CONH2 and CN are particularly unstable. ... 

The alkylation of nitraminopyridines (p. 182) and their acid-catalysed rearrangements to amino-nitropyridines (p. 172) have been described. It was noted that 3-nitraminopyridines do not rearrange (p. 172). The behaviour of... 

The reduction of some amino-nitropyridines with stannous chloride and hydrochloric acid is accompanied by nuclear chlorination (p. 227). This difficulty can be avoided by the use of sodium hydrosulphite, a method which also has the feature of not removing halogen substituents ... 

Here again the question of reactive species in the acidic medium remains open. It must be noted that bromination of 2-amino-5-methyl-pyridine (pK = 7) and 2-amino-5-nitropyridine (pJC = 2.8) in N sulfuric acid takes place on the free base (443). 

Derivatives such as 3-fluoro-4-nitropyridine [13505-01 -6] (396) or the 1-oxide [769-54-0] (397) have been used to characteri2e amino acids and peptides. 5-Eluoro-3-pyridinemethanol [22620-32-2] has been patented as an antihpolytic agent (398). A promising antidepressant, l-(3-fluoro-2-pyridyl)pipera2ine hydrochloride [85386-84-1] is based on 2-chloro-3-fluoropyridine [17282-04-1] (399). 

The main reaction of this type has been the reductive cyclization of nitropyridine derivatives carrying an o-amino ester or o-aminocarbonyl substituent. These cyclize in situ via the o-diamino derivative to give pyridopyrazines of known constitution, either for establishment of structure of products obtained in the ambiguous Isay synthesis (see Section 2.15.15.6.1), or in the synthesis of aza analogues of biologically active molecules. 

However, attempts to prepare 3-iiitro-l,8-iiaphthyridiiie (11) by the Skraup reaction—heating of 2-amino-5-nitropyridine with glycerol in the presence of an oxidant— were not successful (74YZ1328). 

Treatment of 2-amino-3-hydroxypyridine (185) with 2-chloro-3-nitropyridine (193) easily provided intermediate 194. Attempts to cyclize 194 with potassium hydroxide in aqueous ethanolic solutions failed, probably due to strong H-bonding. Similarly as with phenoxazines, the cyclization smoothly proceeded in DMSO to give low yield (31%) of 1,9-diazaphenoxazine (195) (Scheme 30) (74CC878, 76JHC107, 77H391). 

Direct aminadon of 3-nitropyridines v/ith methoxyamine in the presence of zinc chloride under basic conthdons proceeds to give 3-amino amino-3-nitropyridines fEq 9 51 ... 

Reaction of nitroketene animals with enaminoketones provides a route for the derivatives of 2-amino-3-nitropyridines (Eq. 10.87).147... 

The hydrochloride of 3-amino-4-hydrazinopyridine 65 was prepared by reaction of the 4-chloro-3-nitropyridine derivative with ethoxycarbonyl-hydrazine in phenol to give the hydrochloride of ethyl 3-(3-nitro-4-pyridyl)carbazate 64 (R2 = OEt), which on successive heating in concentrated hydrochloric acid and hydrogenation over Pd/C gave 65. Its reaction with phenylacetic acid or with phenoxyacetic acid gave the hydrochloride... 

By this method of preparation 2,3-diaminopyridine is obtained in 26-43% yield from the readily available 2-aminopyridine. The intermediates 2-amino-S-bromopyridine and 2-amino-S-bromo-3-nitropyridine are prepared in higher yields than previously recorded. 

Methods of preparation of 2,3-diaminopyridine which involve the reduction of 2-amino-3-nitropyridine are laborious. The material is obtained in yields of less than 10% by nitration of... 

N-Amination of amines by hydroxyl-amine-O-sulfonic add, 43, 1 p-Aminoacetanilide, oxidation to 4,4 -diaminoazobenzene, 40, 18 2-Amino-5-bromo-3-nitropyridine, 44,... 

C. 2,3-Diamino-5-bronto pyridine (Note 8). A 100-ml. flask fitted with a reflux condenser is charged with 10.9 g. (0.05 mole) of 2-amino-5-bromo-3-nitropyridine, 30 g. of reduced iron, 40 ml. of 95% ethanol, 10 ml. of water, and 0.5 ml. of concentrated hydrochloric acid (Notes 9 and 10). The mixture is heated on a steam bath (Note 11) for 1 hour, and at the end of this period the iron is removed by filtration and is washed three times with 10-ml. portions of hot 95% ethanol. The filtrate and washings are evaporated to dryness, and the dark residue is recrystallized from 50 ml. of water, 1 g. of activated carbon being used and the mixture being filtered while hot. The charcoal is washed with hot ethanol to avoid losses. 2,3-Diamino-5-bromopyridine crystallizes as colorless needles, m.p. 163°. The yield is 6.5-7.1 g. (69-76%). 

Pure 2-amino-5-bromo-3-nitropyridine, yellow needles, m.p. 210°, may be obtained by recrystallizing the product from ethyl methyl ketone. 

Diaminopyridine has been prepared by reduction of 2-amino-3-nitropyridine with iron and aqueous acidified ethanol,3 tin and hydrochloric acid,6 or stannous chloride and hydrochloric acid,6 by catalytic reduction of 3-amino-2-nitropyridine,6 by reduction of 3-amino-2-nitropyridine,7 2-amino-5-chloro-3-nitro-pyridine,8 or 2-amino-5-bromo-3-nitropyridine 4 with sodium hydroxide solution and an aluminum nickel alloy, and by catalytic reduction of 2-amino-5-bromo-3-nitropyridine.4 Animation of... 

Nitropyridine yields a mixture of 2-, 4- and 6-amino-3-nitropyridines by this method142. An amino group is introduced into the 2-position of l,n-dinitronaphthalenes (.n = 3-8)143 and various 5- and 8-nitroquinolines, such as 8-methyl-5-nitroquinoline and 6-chloro-8-nitroquinoline, have been aminated adjacent to the nitro group144. Pteridines are converted into alkylarnino derivatives by the action of a solution of potassium permanganate in an alkylamine, e.g. equation 51145. 

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